Rashid Mohammed H, Rajanna Chythanya, Zhang Dalin, Pasquale Vincenzo, Magder Laurence S, Ali Afsar, Dumontet Stefano, Karaolis David K R
Department of Epidemiology and Preventive Medicine, University of Maryland School of Medicine, Baltimore, MD 21201, USA.
FEMS Microbiol Lett. 2004 Jan 15;230(1):105-13. doi: 10.1016/S0378-1097(03)00879-6.
Vibrio cholerae, the causative agent of cholera can produce an exopolysaccharide (EPS). Some strains can also phenotypically switch from a smooth to a 'rugose' phenotype characterized by small wrinkled colonies, overproduction of EPS, increased biofilm formation in vitro and increased resistance to various stressful conditions. High frequency switching to the rugose phenotype is more common in epidemic strains than in non-pathogenic strains, suggesting EPS production and the rugose phenotype are important in cholera epidemiology. VpsR up-regulates Vibrio polysaccharide (VPS) genes and the synthesis of extracellular EPS (VPS). However, the function of VPS, the rugose phenotype and VpsR in pathogenesis is not well understood. We report that rugose strains of both classical and El Tor biotypes of epidemic V. cholerae are defective in the in vitro production of extracellular collagenase activity. In vivo studies in rabbit ileal loops suggest that VpsR mutants are attenuated in reactogenicity. Intestinal colonization studies in infant mice suggest that VPS production, the rugose phenotype and VpsR have a role in pathogenesis. Our results indicate that regulated VPS production is important for promoting in vivo biofilm formation and pathogenesis. Additionally, VpsR might regulate genes with roles in virulence. Rugose strains appear to be a subpopulation of cells that might act as a 'helper' phenotype promoting the pathogenesis of certain strains. Our studies provide new insight into the potential role of VPS, the rugose phenotype and VpsR in the pathogenesis of epidemic V. cholerae.
霍乱弧菌是霍乱的病原体，可产生一种胞外多糖（EPS）。一些菌株还能从光滑表型转变为“皱缩”表型，其特征是菌落小且有褶皱、EPS过量产生、体外生物膜形成增加以及对各种应激条件的抵抗力增强。在流行菌株中，高频转变为皱缩表型比在非致病菌株中更常见，这表明EPS的产生和皱缩表型在霍乱流行病学中很重要。VpsR上调霍乱弧菌多糖（VPS）基因以及细胞外EPS（VPS）的合成。然而，VPS、皱缩表型和VpsR在发病机制中的功能尚不清楚。我们报告，霍乱弧菌流行株的经典生物型和埃尔托生物型的皱缩菌株在体外产生细胞外胶原酶活性方面存在缺陷。在兔回肠袢中的体内研究表明，VpsR突变体的反应原性减弱。在幼鼠中的肠道定殖研究表明，VPS的产生、皱缩表型和VpsR在发病机制中起作用。我们的结果表明，受调控的VPS产生对于促进体内生物膜形成和发病机制很重要。此外，VpsR可能调控与毒力相关的基因。皱缩菌株似乎是细胞的一个亚群，可能作为一种“辅助”表型促进某些菌株的发病机制。我们的研究为VPS、皱缩表型和VpsR在霍乱弧菌流行株发病机制中的潜在作用提供了新的见解。
